Inter-molecular interactions are a fundamental phenomenon in biology and underlie processes ranging from enzymatic activity and regulation to cell signaling, molecular recognition, and transport. A group of 8 major and 4 minor users from Weill Cornell Medical College (WCMC) participate in the current application to acquire an isothermal titration calorimeter (ITC) in order to characterize the thermodynamic bases of a broad range of molecular interactions. Their research interest include protein: protein interactions underlying cell signaling cascades, viral infection, protein translation and folding;protein: membrane interactions, mediating folding;amphiphile: membrane interactions, alerting bilayer physical properties;development of RNA aptamers as genetically encoded analyte sensors;and trans-membrane transport of ions and other solutes. The impact of such studies on major progress in biomedical sciences is reflected in the extensive funding that the NIH has awarded to the participating researchers, which include Eliezer, Lu, Radhakrishnan and Wu from the Biochemistry Department;Andersen, Blanchard, Boudker, Huang, Weinstein from the Department of Physiology and Biophysics, Accardi and Nimigean from the Department of Anesthesiology and Jeffery from the Pharmacology Department. ITC is based on the measurements of heat, released or absorbed upon complex formation, and provides a universal, label-free, rapid and reliable means to (i) detect interactions;(ii) distinguish between different modes of binding;and (iii) obtain the thermodynamic parameters of binding such as the Gibbs free energy, enthalpy, entropy and heat capacity. Several researchers participating in this application have extensive experience in using ITC and have employed it in studies published in peer reviewed high impact journals. However, current work is impeded because no such instrument exists at WCMC. To eliminate these impediments and increase productivity and creativity of the NIH-supported research efforts, we request funding to purchase an Auto-iTC200 instrument, which is state of the art equipment produced by Microcal, now part of GE Healthcare. For this purpose we request a total of $310,931, which includes funding for the instrument acquisition, software licenses and a two-year service contract.